Alsiraj Yasir, Huang Hong, Shoemaker Robin, Schanbacher Brandon, Murphy Margaret, Giannone Peter, Bauer John A
Department of Pediatrics, College of Medicine, University of Kentucky, 138 Leader Ave, Lexington, KY 40536-0200, USA.
Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536-0200, USA.
Nutrients. 2025 Apr 26;17(9):1464. doi: 10.3390/nu17091464.
The long-term effects of a perinatal high-fat diet on the cardiovascular function of offspring are not well elucidated. We hypothesize that perinatal exposure to a high-fat diet alters adult cardiovascular and immune responses in a sex-specific manner. Male and female offspring were born to perinatal high-fat (pHFD) or control diet (pCD)-fed C57BL/6 mothers and weaned to a control diet. Cardiovascular function (baseline and response to an acute isoproterenol stress test) was quantified at 8 weeks of age, and acute blood inflammatory response to a single low dose of lipopolysaccharide at 9 weeks of age. Male pHFD offspring had identical baseline cardiovascular function compared to pCD mice but a blunted response to isoproterenol (20-45% reductions in cardiac output, stroke volume, and left ventricular fractional shortening). In contrast, baseline cardiovascular parameters were reduced in female pHFD compared to pCD offspring, but there was no effect of perinatal diet on response to isoproterenol. Concentrations of TNF-α and IL-6 in plasma two hours after a low-dose LPS administration were highest in female pCD mice. Perinatal high-fat diet exposure resulted in sex-specific adaptations in cardiovascular function and immune response. Female offspring displayed baseline impairments, whereas male offspring showed latent vulnerability under stress. These differences may reflect underlying hormonal or epigenetic mechanisms that diverge by sex. Future studies should examine the roles of sex hormones and gene regulation pathways to better understand these dimorphic outcomes. These findings emphasize the importance of maternal diet in shaping offspring cardiometabolic risks and highlight potential avenues for nutritional interventions during pregnancy.
围产期高脂饮食对后代心血管功能的长期影响尚未得到充分阐明。我们假设围产期暴露于高脂饮食会以性别特异性方式改变成年后的心血管和免疫反应。雄性和雌性后代由围产期高脂（pHFD）或对照饮食（pCD）喂养的C57BL/6母亲所生，并断奶至对照饮食。在8周龄时量化心血管功能（基线和对急性异丙肾上腺素应激试验的反应），并在9周龄时量化对单次低剂量脂多糖的急性血液炎症反应。与pCD小鼠相比，雄性pHFD后代的基线心血管功能相同，但对异丙肾上腺素的反应减弱（心输出量、每搏输出量和左心室缩短分数降低20-45%）。相比之下，与pCD后代相比，雌性pHFD的基线心血管参数降低，但围产期饮食对异丙肾上腺素反应没有影响。低剂量LPS给药两小时后，雌性pCD小鼠血浆中TNF-α和IL-6的浓度最高。围产期高脂饮食暴露导致心血管功能和免疫反应出现性别特异性适应性变化。雌性后代表现出基线损伤，而雄性后代在应激下表现出潜在的易损性。这些差异可能反映了按性别不同的潜在激素或表观遗传机制。未来的研究应研究性激素和基因调控途径的作用，以更好地理解这些二态性结果。这些发现强调了母亲饮食在塑造后代心脏代谢风险方面的重要性，并突出了孕期营养干预的潜在途径。
